US11359112B2 - Coatings with tunable amine density - Google Patents

Coatings with tunable amine density Download PDF

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US11359112B2
US11359112B2 US16/348,485 US201716348485A US11359112B2 US 11359112 B2 US11359112 B2 US 11359112B2 US 201716348485 A US201716348485 A US 201716348485A US 11359112 B2 US11359112 B2 US 11359112B2
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array
amino
alkyl
molecules
substituted
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US20190359854A1 (en
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Gaurav Saini
David Smith
Patrick Walsh
Jae H. Park
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Cowper Sciences Inc
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    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
    • C09D183/00—Coating compositions based on macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon, with or without sulfur, nitrogen, oxygen, or carbon only; Coating compositions based on derivatives of such polymers
    • C09D183/04—Polysiloxanes
    • C09D183/08—Polysiloxanes containing silicon bound to organic groups containing atoms other than carbon, hydrogen, and oxygen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804—Compounds having Si-O-C linkages
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D1/00—Processes for applying liquids or other fluent materials
    • B05D1/60—Deposition of organic layers from vapour phase
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0834—Compounds having one or more O-Si linkage
    • C07F7/0838—Compounds with one or more Si-O-Si sequences
    • C07F7/087—Compounds of unknown structure containing a Si-O-Si sequence
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F30/00—Homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal
    • C08F30/04—Homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal containing a metal
    • C08F30/08—Homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal containing a metal containing silicon
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
    • C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
    • C08G65/32—Polymers modified by chemical after-treatment
    • C08G65/329—Polymers modified by chemical after-treatment with organic compounds
    • C08G65/336—Polymers modified by chemical after-treatment with organic compounds containing silicon
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
    • C08G77/04—Polysiloxanes
    • C08G77/14—Polysiloxanes containing silicon bound to oxygen-containing groups
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
    • C08G77/04—Polysiloxanes
    • C08G77/22—Polysiloxanes containing silicon bound to organic groups containing atoms other than carbon, hydrogen and oxygen
    • C08G77/26—Polysiloxanes containing silicon bound to organic groups containing atoms other than carbon, hydrogen and oxygen nitrogen-containing groups
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
    • C09D143/00—Coating compositions based on homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing boron, silicon, phosphorus, selenium, tellurium, or a metal; Coating compositions based on derivatives of such polymers
    • C09D143/04—Homopolymers or copolymers of monomers containing silicon
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/544—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports

Definitions

  • the molecules or salts of structure I can comprise a solid phase.
  • the solid phase can comprise a silicon atom.
  • molecules or salts thereof having the structure:
  • the carbon center can be in an R-configuration. In some aspects, the carbon center can be in an S-configuration. In some aspects are molecules or salts comprising a solid phase. In some aspects the solid phase can comprise a silicon atom. In some aspects are molecules of structure II, wherein R 3 can comprise alkyl, aminoheteroalkyl, polyamidoaminoalkyl, or polyaminoalkyl.
  • molecules or salts thereof having the structure:
  • a carbon center can be in an R-configuration. In some aspects, the carbon center can be in an S-configuration. In some aspects the molecules or salts of structures III, IV, V, or VI can comprise a solid phase. In some aspects, the solid phase can comprise a silicon atom.
  • the method can comprise forming an oxygen-silicon covalent bond between a solid substrate and a first molecule.
  • the first molecule can comprise a silicon at a first end and an epoxide, isocyanate, or thioisocyanate at a second end.
  • the method can further comprise forming a Y-carbon covalent bond between a carbon atom of an epoxide, isocyanate, or thioisocyanate and a second molecule comprising an amino group.
  • Y can be nitrogen, oxygen, sulfur, or selenium.
  • the epoxide, isocyanate, or isothiocyanate and silicon can be linked by a group comprising an alkyl, alkylether, or alkylthioether, wherein each of alkyl, alkylether, or alkylthioether is optionally substituted with hydroxyl, thiol, amino, or halo.
  • the second molecule can be an alkylamine, heteroalkylamine, amino-substituted alkylamine, amino-substituted heteroalkylamine, amidoalkylamine, amidoheteroalkylamine, or amino-substituted amidoheteroalkylamine, each optionally substituted with an alkyl, heteroalkyl, amino-substituted alkyl, amino-substituted heteroalkyl, amidoalkyl, amidoheteroalkyl, or amino-substituted amidoheteroalkyl.
  • forming an oxygen-silicon bond can comprise a deposition reaction.
  • a deposition reaction can be performed in the gas phase.
  • the deposition reaction can comprise a chemical vapor deposition reaction.
  • the chemical vapor deposition reaction can occur at an elevated temperature.
  • the elevated temperature can be at least about 100° C., 110° C., 120° C., 130° C., 140° C., or 150° C.
  • the first molecule can be 3-glycidoxypropyltrimethoxysilane (GPTMS) or any reactive aminosilane.
  • the second molecule can be ethylenediamine (EDA), (ethylenedioxy)bis(ethylamine) (EDBA), tris (2-aminoethyl)amine (TAEA), polyamidoamine (PAMAM), or polyallylamine (PAAm).
  • PAAm can have an average molecular weight of from about 1 KDa to about 100 KDa.
  • the second molecule can have a boiling point of from about 100° C. to 300° C.
  • the method can further comprise coupling the amino group to a protected amino acid or salt thereof.
  • the protected amino acid salt can be a tert-butyl carbamate (Boc)- or 9-fluorenylmethyl carbamate (Fmoc)-protected amino acid.
  • the amino acid can be glycine.
  • amino coatings comprising two or more of any one of the molecules or salts of structures I, II, III, IV, V, or VI.
  • methods of tuning the amino group density of the amino coating are arrays comprising two or more of any one of the molecules or salts of structures I, II, III, IV, V, or VI.
  • the array can comprise at least 2 of any one of the molecules or salts of structures I, II, III, IV, V, or VI.
  • the array can comprise a density of said amino groups from about 1 ⁇ 10 10 groups per cm 2 to about 1 ⁇ 10 14 groups per cm 2 .
  • molecules can be stereoenriched or racemtates.
  • molecules or salts can have an enantiomeric excess of at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%.
  • at least one of the molecules or salts can form a coating.
  • the coating has a thickness of from about 1 angstrom to about 25 angstroms.
  • molecules or their salts are cross-linked.
  • arrays can further comprise instructions for their use.
  • kits for making an array.
  • making an array can comprise associating the molecule or salt of structure I, II, III, IV, V, or VI with a substrate.
  • making an array can comprise any of the methods disclosed herein for making molecules or salts of structures I, II, III, IV, V, or VI.
  • the array comprises a density of amino group about 1 ⁇ 10 10 groups per cm2 to about 1 ⁇ 10 14 groups per cm2.
  • methods comprising tuning the density of said amino groups on said array.
  • kits comprise the molecules of structures I, II, III, IV, V, or VI.
  • kits comprise a binding moiety.
  • a binding moiety can be an antibody.
  • a binding moiety can emit a signal.
  • kits In some aspects are methods of making kits. In some aspects, methods of making kits can comprise forming a kit with the molecules or salts of structures I, II, III, IV, V, VI. In some aspects are molecules or salts made by the process of the methods disclosed herein. In some aspects are arrays made by the process of the methods disclosed herein.
  • FIG. 1 depicts a GPTMS-PAAm surface coating, prepared by chemical vapor deposition.
  • GPTMS is 3-glycidoxypropyltrimethoxysilane.
  • FIG. 2 depicts a GPTMS-TAEA surface coating prepared by chemical vapor deposition.
  • FIG. 3 depicts the reactive amine density of GPTMS-TAEA surface coatings prepared by either solution phase reaction or chemical vapor deposition.
  • FIG. 4 Depicts the reactive amine density of GPTMS-TEA coating compared to a GPTMS coating.
  • FIG. 5 depicts a GPTMS-HMDA linker prepared by chemical vapor deposition
  • FIG. 6 Depicts reactive amine densities for GPTMS-linked EDA, TAEA, PAMAM, and PAAm amino coatings. Also depicted are reactive amine densities for aminosilane coatings APTES, APDEMS, and APDIPES.
  • FIG. 7 reactive amine densities for GPTMS-TAEA linkers with chemical vapor deposition performed at 100, 125, and 150 degrees Celcius.
  • FIG. 8 depicts reactive amine densities from GPTMS-linked EDA, TAEA, and PAAm surface coatings.
  • FIG. 9 depicts water contact angle and thickness properties for GPTMS-linked-EDA and Boc-Gly surface coatings at different deposition conditions.
  • FIG. 10 depicts surface amine densities of GPTMS-TAEA, GPTMS-PAAm, and APTES surface coatings.
  • FIG. 11 depicts the use of a diluent to tune the reaction of forming second coating layer.
  • FIG. 12 depicts the experimental conditions for use of a diluent to tune the reaction of forming a second coating layer.
  • FIG. 13 depicts thickness and water contact angle analysis of amino coatings produced with a diluent in the formation of the second coating layer.
  • FIG. 14 depicts reactive amine density of amino coatings under various reaction conditions.
  • FIG. 15 depicts the use of a molecular array for immunosignaturing.
  • FIG. 16 depicts the arrangement of features on a molecular array.
  • FIG. 17 depicts substrate characteristics, coating compositions, deposition methods, and analytical characterization methods.
  • FIG. 18 depicts a scheme for peptide synthesis.
  • FIG. 19 depicts protected amino acids.
  • FIG. 20 depicts aminosilane coating structures.
  • FIG. 21 depicts why surface properties control important.
  • FIG. 22 depicts thickness and water contact angle analysis of amino coatings.
  • FIG. 23 depicts a scheme for a reactive amine density assay.
  • FIG. 24 depicts an amine density analysis of amino coatings.
  • FIG. 25 depicts an AFM analysis of the smoothness of deposition of amino coatings.
  • FIG. 26 depicts an experimental process for side chain deprotection.
  • FIG. 27 depicts an outline of a peptide synthesis process.
  • FIG. 28 depicts a thickness analysis of peptide-functionalized amino coatings.
  • FIG. 29 depicts thickness and XPS analysis of amino coatings.
  • FIG. 30 depicts a scheme for peptide synthesis, amine capping, and MALDI-MS analysis.
  • FIG. 31 depicts a scheme for peptide synthesis, amine capping, and MALDI-MS analysis.
  • FIG. 32 depicts a thickness analysis of amino coatings.
  • FIG. 33 depicts a thickness analysis of amino coatings.
  • FIG. 34 depicts procedures for surface preparation for MALDI-MS analysis.
  • FIG. 35 depicts a MALDI-MS analysis of array coatings.
  • FIG. 36 depicts a purity analysis of peptides synthesized on amino coatings.
  • FIG. 37 depicts a MALDI-MS analysis of array coatings.
  • FIG. 38 depicts a purity analysis of peptides synthesized on amino coatings.
  • FIG. 39 depicts a MALDI-MS analysis of array coatings.
  • FIG. 40 depicts a purity analysis of peptides synthesized on amino coatings.
  • FIG. 41 depicts a MALDI-MS analysis of array coatings.
  • FIG. 42 depicts a purity analysis of peptides synthesized on amino coatings.
  • FIG. 43 depicts a summary of amino coating properties.
  • the term “about” or “approximately” can mean within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e. the limitations of the measurement system. For example, “about” can mean within 1 or more than 1 standard deviation. Alternatively, “about” can mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term can mean within an order of magnitude, within 5-fold, and more preferably within 2-fold, of a value. Where particular values are described in the application and claims, unless otherwise stated the term “about” meaning within an acceptable error range for the particular value should be assumed. The term “about” has the meaning as commonly understood by one of ordinary skill in the art. In some embodiments, the term “about” refers to ⁇ 10%. In some embodiments, the term “about” refers to ⁇ 5%.
  • the disclosure in one aspect, relates to compounds, methods, and devices that identify differential patterns of peripheral-blood antibody binding to a array-bound molecular library. Differential binding of patient samples to the array results in specific binding patterns or signatures indicative of the disease state of the patient. These binding signatures can accurately determine or diagnose a disease activity, including but not limited to autoimmune disease activity, infectious disease activity, cancer activity, and diabetes disease activity.
  • arrays with chemical libraries produced by the technologies disclosed herein are used for immune-based diagnostic assays, for example, immunosignature assays.
  • immunosignature assays using a patient's antibody repertoire from a drop of blood bound to the arrays, a fluorescence binding profile image of the bound array provide sufficient information to identify and classify a disease state.
  • the arrays disclosed herein incorporate analytical measurements capability within each synthesized array using orthogonal analytical methods including ellipsometry, mass spectrometry, and fluorescence. These measurements enable longitudinal qualitative and quantitative assessment of array synthesis performance.
  • detection of antibody binding on a peptide array poses some challenges that can be addressed by the technologies disclosed herein.
  • the technologies disclosed herein address two potential shortcomings of using molecular arrays to profile antibody binding. First, non-specific antibody binding on a array is minimized by coating the solid support with a moderately hydrophilic monolayer comprising, in some embodiments, polyethylene glycol. In some embodiments, the hydrophilic monolayer is homogeneous. Second, synthesized library are linked to the surface using a linker that moves the peptide away from the surface of the solid support so that the peptide may be presented to an antibody in an unhindered orientation.
  • the technologies disclosed herein include such linkers, which, in one aspect, connect chemical libraries to solid supports, including, in some aspects, arrays for immunosignaturing.
  • Molecules or linkers can also be known as coatings when, for example, formed on a solid support.
  • the technologies herein relate to methods for synthesizing amino-containing coatings, which can be further functionalized at the amino group.
  • the technologies herein further relate to methods for tuning the density of amino groups in coatings. Tuning the density of amino groups in coatings has the advantage of providing flexibility for optimizing the binding characteristics of coatings, and functionalized coatings, to binding moieties.
  • Formation of coatings onto a solid phase can be achieved by solution phase or gas phase reactions.
  • Solid phases can comprise native oxide, thermal oxide, or siloxane surfaces.
  • Solid phases can comprise BTMSE.
  • arrays comprising the molecules disclosed herein.
  • the arrays comprise a nucleoside, nucleotide, polynucleotide, peptide, peptoid, saccharide, aptamer, or antibody or fragment thereof chemically bound to the linker.
  • the nucleoside, nucleotide, polynucleotide, peptide, peptoid, saccharide, aptamer, or antibody or fragment thereof comprise a chemical library.
  • the array is a peptide array.
  • the peptide array is synthesized in situ.
  • the technologies include qualitative in situ mass spectrometry of synthesized peptides directly from solid support. Mass spectrometry is performed by incorporating a gas-phase cleavable linker between the solid support and the synthesized peptides so that cleavage of the peptide is done without diffusion from the array feature.
  • Matrix-Assisted Laser Desorption Ionization (MALDI) mass spectrometry is performed directly on the solid support by applying a thin aerosol matrix layer and subsequently focusing the MALDI laser on individual peptide features to acquire a mass spectrum for each synthesized peptide.
  • MALDI Matrix-Assisted Laser Desorption Ionization
  • Qualitative in situ MALDI mass spectrum from a peptide array feature produced using the photolithographic synthesis approach are also included in the methods and devices described herein.
  • Other analyses known to those of skill in the art may also be used to quantify and/or qualify the fidelity of the in situ synthesis process disclosed herein.
  • attach refers to covalent interactions (e.g., by chemically coupling), or non-covalent interactions (e.g., ionic interactions, hydrophobic interactions, hydrogen bonds, hybridization, etc.).
  • specific refers to the preferential recognition, contact, and formation of a stable complex between a first molecule and a second molecule compared to that of the first molecule with any one of a plurality of other molecules (e.g., substantially less to no recognition, contact, or formation of a stable complex between the first molecule and any one of the plurality of other molecules).
  • two molecules may be specifically attached, specifically bound, specifically coupled, or specifically linked.
  • binding may refer to either a specific interaction, such as the interaction of an antibody with an epitope, or it may refer to a non-specific interaction.
  • alkyl as employed herein alone or as part of another group can include both straight and branched chain hydrocarbons, containing, for instance, 1 to 20 carbons, 1 to 10 carbons, or 1 to 8 carbons, in the normal chain, such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, isobutyl, pentyl, hexyl, isohexyl, heptyl, 4,4-dimethylpentyl, octyl, 2,2,4-trimethyl-pentyl, nonyl, decyl, undecyl, dodecyl, the various branched chain isomers thereof, and the like as well as such groups including 1 to 4 substituents such as halo, for example F, Br, Cl or I or CF 3 , alkyl, alkoxy, aryl, aryloxy, aryl(aryl) or diaryl, ary
  • cycloalkyl as employed herein alone or as part of another group can include saturated or partially unsaturated (containing 1 or 2 double bonds) cyclic hydrocarbon groups containing 1 to 3 rings, including monocyclic alkyl, bicyclic alkyl (or bicycloalkyl) and tricyclic alkyl (tricycloalkyl), containing a total of 3 to 20 carbons forming the ring and which may be fused to 1 or 2 aromatic rings as described for aryl, which includes cyclopropyl, cyclobuyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl and cyclododecyl, cyclohexenyl, adamantyl, and the like, any of which may be optionally substituted with 1 to 4 substituents such as halogen, alkyl, alkoxy, hydroxyl, aryl, aryloxy,
  • alkanoyl as used herein alone or as part of another group can refer to alkyl linked to a carbonyl group.
  • alkenyl as used herein by itself or as part of another group can refer to straight or branched chain radicals of, for instance, 2 to 20 carbons in the normal chain, which include one to six double bonds in the normal chain, such as vinyl, 2-propenyl, 3-butenyl, 4-pentenyl, 3-pentenyl, 2-hexenyl, 3-hexenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 3-octenyl, 3-nonenyl, 4-decenyl, 3-undecenyl, 4-dodecenyl, 4, 8, 12-tetradecatrienyl, and the like, and which may be optionally substituted with 1 to 4 substituents, namely, halogen, haloalkyl, alkyl, alkoxy, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, amino, hydroxyl, heteroaryl
  • alkynyl as used herein by itself or as part of another group can refer to straight or branched chain radicals of 2 to 20 carbons in the normal chain, which include one triple bond in the normal chain, such as 2-propynyl, 3-butynyl, 2-butynyl, 4-pentynyl, 2-hexynyl, 3-hexynyl, 2-heptynyl, 3-heptynyl, 4-heptynyl, 3-octenyl, 3-nonenyl, 4-decenyl, 3-undecenyl, 4-dodecenyl and the like, and which may be optionally substituted with 1 to 4 substituents, namely, halogen, haloalkyl, alkyl, alkoxy, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, amino, heteroaryl, cycloheteroalkyl, hydroxy
  • halogen or “halo” as used herein alone or as part of another group can refer to chlorine, bromine, fluorine, and iodine.
  • aryl as employed herein alone or as part of another group can refer to monocyclic and biclic aromatic groups containing 6 to 10 carbons in the ring portion (such as phenyl or naphthyl including 1-naphthyl and 2-naphthyl) and may optionally include one to three additional rings fused to a carbocyclic ring or a heterocyclic ring (such as aryl, cycloalkyl, heteroaryl or cycloheteroalkyl rings) and may be optionally substituted through available carbon atoms with 1, 2, or 3 groups selected from hydrogen, halo, haloalkyl, alkyl, alkoxy, haloalkoxy, alkenyl, trifluoromethyl, trifluoromethoxy, alkynyl, cycloalkylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl, aryl, heteroaryl, arylalky
  • amino-substituted as employed herein alone or as part of another group can refer to a chemical group having from 1 to 10 amino groups substituted thereon.
  • alkylthio also known as “thioalkyl” or “arylthio” (also known as “thioaryl”) as employed herein alone or as part of another group can include any of the above alkyl or aryl groups linked to a sulfur atom.
  • heteroalkyl as employed herein alone or as part of another group can include any of the above alkyl groups linked to a selenium atom.
  • alkylamino or “arylamino” as employed herein alone or as part of another group can include any of the above alkyl or aryl groups linked to a nitrogen atom.
  • acyl as employed herein by itself as part of another group, as defined herein, can refer to an organic radical linked to a carbonyl
  • acyl groups include any of the R groups attached to a carbonyl, such as alkanoyl, alkenoyl, aroyl, aralkanoyl, heteroaroyl, cycloalkanoyl, cycloheteroalkanoyl and the like.
  • cycloheteroalkyl as used herein alone or as part of another group can refer to a 5-, 6-, or 7-membered saturated or partially unsaturated ring which can include 1 to 2 heteroatoms such as nitrogen, oxygen and/or sulfur, linked through a carbon atom or a heteroatom, where possible, optionally via the linker (CH 2 ), (where r is 1, 2, or 3).
  • heteroaryl as used herein alone or as part of another group can refer to a 5- or 6-membered aromatic ring which can include 1, 2, 3 or 4 heteroatoms such as nitrogen, oxygen or sulfur, and such rings fused to an aryl, cycloalkyl, heteroaryl or cycloheteroalkyl ring, and includes possible N-oxides.
  • the heteroaryl group may optionally include 1 to 4 substituents such as any of the substituents set out above for alkyl.
  • heteroalkyl as used herein alone or as part of another group can refer to an alkyl group, as defined herein, which can include 1, 2, 3, or 4 heteroatoms such as nitrogen, oxygen or sulfur.
  • the heteroalkyl group may optionally include 1 to 4 substituents such as any of the substituents set out above for alkyl.
  • Compounds can have asymmetric carbon centers at any of the carbon atoms including any one of the R substituents.
  • Compounds can be either optically active or optically inactive.
  • Asymmetric carbon centers can be independently in an R- or S-configuration.
  • asymmetric carbons are carbons that are a stereogenic center. Consequently, compounds of structures I, IA, or II can exist in enantiomeric or diastereomeric forms or in mixtures thereof.
  • Enantiomeric mixtures can exist with an enantiomeric excess of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100%.
  • Diastereomeric mixtures can exist with a diastereomeric ratio of 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 20:1, 50:1, 100:1, or 500:1.
  • the processes for preparation of the molecules disclosed herein can utilize racemates, enantiomers or diastereomers as starting materials. When diastereomeric or enantiomeric products are prepared, they can be separated by conventional methods, for example, by chromatographic or fractional crystallization.
  • a polynucleotide can be any type of nucleic acid molecule, including DNA, RNA, a hybridization thereof, or any combination thereof.
  • a polynucleotide can be cDNA, genomic DNA, mRNA, tRNA, rRNA, or microRNA.
  • a peptide, polypeptide, or protein can be contemplated to include any fragments thereof, in particular, immunologically detectable fragments.
  • a peptide can be contemplated to include an ⁇ -peptide, a ⁇ -peptide, or a ⁇ -peptide.
  • Methods disclosed herein can include synthesizing coatings on solid supports. Characteristics of coatings prepared by the methods disclosed herein can be analyzed by various methods understood by person of skill in the art. Methods of analysis can include, ellipsometry, water contact angle (WCA), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), colorimetry, mass-spectrometry, including MALDI-MS, and the like.
  • forming coatings can comprise coupling an aminosilane to a substrate.
  • the aminosilane can comprise 3-aminopropyltriethoxysilane (APTES), 3-aminopropylmethyldiethoxysilane (APDEMS), or 3-aminopropyldiisopropylethoxysilane (APDIPES).
  • forming coatings can comprise a first step comprising forming a first coating layer.
  • the first step can comprise forming an oxygen-silicon bond between a sold substrate and a first molecule.
  • the first molecule can comprise a silicon at a first end and an epoxide, isocyanate, or thioisocyanate at a second end.
  • the first step can be performed in solution phase or in gas phase.
  • forming coatings can further comprise a second step comprising coupling a second molecule to the epoxide, isocyante, or thioisocyanate of the first molecule to form a second coating layer.
  • Coatings can be understood to encompass both single layer coatings and coatings comprising a first layer and a second layer.
  • the second molecule can have a boiling point of about 100° C., 110° C., 120° C., 130° C., 140° C., 150° C., 160° C., 170° C., 180° C., 190° C., 200° C., 210° C., 220° C., 230° C., 240° C., 250° C., 260° C., 270° C., 280° C., 290° C., 300° C., 310° C., 320° C., 330° C., 340° C., or 350° C.
  • the second step can comprise using a diluent.
  • a diluent can be an alcohol.
  • the alcohol can be ethanol, 1-propanol, 2-propanol (also known as isopropanol), 1-butanol, 2-butanol, tert-butanol, 1-pentanol, 2-pentanol, 3-pentanol, 3-methylbutan-1-ol (also known as isoamyl or isopentyl alcohol), 2-methylbutan-1-ol, 2,2-dimethylpropan-1-ol (also known as neopentyl alcohol), 3-methylbutan-2-ol, or 2-methylbutan-2-ol (also known as tert-amyl alcohol).
  • coatings can be characterized by their water contact angle. In some embodiments, coatings can have a water contact angle of about 10°, 20°, 30°, 40°, 50°, 60°, 70°, 80°, 90°, 100°, 110°, 120°, 130°, 140°, 150°, or 160°. In some embodiments, coatings can have a contact angle from about 10° to about 120°. In some embodiments, coatings can have a water contact angle from about 40° to about 90°. In some embodiments, coatings can be characterized by their thickness.
  • thickness can be measured by ellipsometry.
  • coatings can have a thickness of about 0.5 angstroms ( ⁇ ), 0.6 ⁇ , 0.7 ⁇ , 0.8 ⁇ , 0.9 ⁇ , 1 ⁇ , 2 ⁇ , 3 ⁇ , 4 ⁇ , 5 ⁇ , 6 ⁇ , 7 ⁇ , 8 ⁇ , 9 ⁇ , 10 ⁇ , 11 ⁇ , 12 ⁇ , 13 ⁇ , 14 ⁇ , 15 ⁇ , 16 ⁇ , 17 ⁇ , 18 ⁇ , 19 ⁇ , 20 ⁇ , 25 ⁇ , 30 ⁇ , 35 ⁇ , 40 ⁇ , 45 ⁇ , 50 ⁇ , 60 ⁇ , 70 ⁇ , 80 ⁇ , 90 ⁇ , or 100 ⁇ .
  • coatings can have a thickness of from about 1 ⁇ to about 10 ⁇ . In some embodiments, coatings can have a thickness of from about 5 ⁇ to about 7 ⁇ . In some embodiments, coatings can be characterized by their smoothness. In some embodiments, coating smoothness can be measured by AFM.
  • coatings can have a smoothness of a root mean square of roughness (R q ) of about 0.10 nm, 0.11 nm, 0.12 nm, 0.13 nm, 0.14 nm, 0.15 nm, 0.16 nm, 0.17 nm, 0.18 nm, 0.19 nm, 0.20 nm, 0.21 nm, 0.22 nm, 0.23 nm, 0.24 nm, 0.25 nm, 0.26 nm, 0.27 nm, 0.28 nm, 0.29 nm, or 0.30 nm.
  • coatings can have an R q of from about 0.1 nm to about 0.3 nm.
  • coatings can have an R q of from about 0.2 to about 0.25 nm. In some embodiments, coatings can have a density of amino groups of about 1 ⁇ 10 9 , 1 ⁇ 10 10 , 1 ⁇ 10 11 , 1 ⁇ 10 12 , 1 ⁇ 10 13 , 1 ⁇ 10 14 , or 1 ⁇ 10 15 amino groups per square centimeter.
  • coatings can be coupled at the amine to a target analyte to form a target analyte-functionalized coating.
  • a target analyte can be a peptide.
  • a peptide can be from about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95,
  • peptides can comprise a library of peptides.
  • peptides can have protected side chains.
  • peptide side chains can be protected as benzyl ethers.
  • a coating can be coupled to a peptide by stepwise coupling of each of amino acid of the peptide.
  • Some embodiments comprise functionalizing an amimo coating.
  • Amino coatings can be functionalized by coupling the amino groups of the amino coating to molecules.
  • a molecule can be a building block.
  • coupling comprises: coupling of an amino group to the carboxylic acid of a first building block.
  • a building block can comprise a carboxylic acid and a protected amine.
  • a building block can be an N-protected amino acid.
  • the protected amino acid can comprise a Boc-protected amine or an Fmoc-protected amine.
  • coupling can further comprise deprotection of the coupled building block.
  • coupling can further comprise coupling of the amino group of the deprotected first building block to the carboxylic acid of a second building block.
  • functionalizing of an amino coating can comprise iterative couplings to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98,
  • functionalizing an amino coating can further comprise performing a capping step after any one of the described coupling steps.
  • Capping can comprise reacting amino groups with a reagent to form a protected, or capped, amino group.
  • Capping can comprise reacting amino groups that were not consumed in the preceding coupling reaction.
  • Capping reagents can comprise acetic anhydride, acetyl chloride, acetyl fluoride, or an acylglycine.
  • the capping step can form an alkylamine, arylamine, acetamide, carbamate, phthalimide, enamine, sulfonamide, or N-protected amino acid.
  • the N-protected amino acid can be an N-acyl-protected amino acid.
  • the protected amino acid can be acetyl glycine.
  • forming coatings can comprise a first step comprising forming a first coating layer.
  • the first step can comprise forming an oxygen-silicon bond between a sold substrate and a first molecule.
  • the first molecule can comprise a silicon at a first end and an epoxide, isocyanate, or thioisocyanate at a second end.
  • the first step can be performed in solution phase or in gas phase.
  • forming coatings can further comprise a second step comprising forming a second coating layer.
  • forming said second coating layer can comprise a chemical vapor deposition reaction.
  • solid supports also known as solid phases, substrates, or supports.
  • the nature and geometry of a support or substrate can depend upon a variety of factors, including the type of array (e.g., one-dimensional, two-dimensional or three-dimensional).
  • a substrate can be composed of any material which will permit coupling of a nucleoside, nucleotide, polynucleotide, peptide, peptoid, saccharide, aptamer, or antibody or fragment thereof, which will not melt or degrade under the conditions used to couple said nucleoside, nucleotide, polynucleotide, peptide, peptoid, saccharide, aptamer, or antibody or fragment thereof to said solid support.
  • a solid support can be composed of any material which will permit coupling of a target analyte, and/or other moiety at one or more discrete regions and/or discrete locations within the discrete regions.
  • a solid support can be composed of any material which will permit washing or physical or chemical manipulation without dislodging a target analyte or binding moiety from the solid support.
  • a substrate may take a variety of configurations ranging from simple to complex, depending on the intended use of the array.
  • a substrate can have an overall slide or plate configuration, such as a rectangular or disc configuration.
  • a standard microplate configuration can be used.
  • the surface may be smooth or substantially planar, or have irregularities, such as depressions or elevations.
  • the substrates of the presently disclosed subject matter can include at least one surface on which a pattern of recombinant virion microspots can be coupled or deposited.
  • a substrate may have a rectangular cross-sectional shape, having a length of from about 10-200 mm, 40-150 mm, or 75-125 mm; a width of from about 10-200 mm, 20-120 mm, or 25-80 mm, and a thickness of from about 0.01-5.0 mm, 0.1-2 mm, or 0.2 to 1 mm.
  • a support may be organic or inorganic; may be metal (e.g., copper or silver) or non-metal; may be a polymer or nonpolymer; may be conducting, semiconducting or nonconducting (insulating); may be reflecting or nonreflecting; may be porous or nonporous; etc.
  • a solid support as described above can be formed of any suitable material, including metals, metal oxides, semiconductors, polymers (particularly organic polymers in any suitable form including woven, nonwoven, molded, extruded, cast, etc.), silicon, silicon oxide, and composites thereof.
  • Suitable materials for use as substrates include, but are not limited to, polycarbonate, gold, silicon, silicon oxide, silicon oxynitride, indium, tantalum oxide, niobium oxide, titanium, titanium oxide, platinum, iridium, indium tin oxide, diamond or diamond-like film, acrylic, styrene-methyl methacrylate copolymers, ethylene/acrylic acid, acrylonitrile-butadiene-styrene (ABS), ABS/polycarbonate, ABS/polysulfone, ABS/polyvinyl chloride, ethylene propylene, ethylene vinyl acetate (EVA), nitrocellulose, nylons (including nylon 6, nylon 6/6, nylon 6/6-6, nylon 6/9, nylon 6/10, nylon 6/12, nylon 11 and nylon 12), polyacrylonitrile (PAN), polyacrylate, polycarbonate, polybutylene terephthalate (PBT), poly(ethylene) (PE) (including low density, linear low density, high density, cross-linked
  • solid supports examples include polypropylene, polystyrene, polyethylene, dextran, nylon, amylases, glass, natural and modified celluloses (e.g., nitrocellulose), polyacrylamides, agaroses and magnetite.
  • the solid support can be silica or glass because of its great chemical resistance against solvents, its mechanical stability, its low intrinsic fluorescence properties, and its flexibility of being readily functionalized.
  • the substrate can be glass, particularly glass coated with nitrocellulose, more particularly a nitrocellulose-coated slide (e.g., FAST slides).
  • the support can be planar. In some instances, the support can be spherical. In some instances, the support can be a bead. In some instances, a support can be magnetic. In some instances, a magnetic solid support can comprise magnetite, maghemite, FePt, SrFe, iron, cobalt, nickel, chromium dioxide, ferrites, or mixtures thereof. In some instances, a support can be nonmagnetic. In some embodiments, the nonmagnetic solid support can comprise a polymer, metal, glass, alloy, mineral, or mixture thereof. In some instances a nonmagnetic material can be a coating around a magnetic solid support. In some instances, a magnetic material may be distributed in the continuous phase of a magnetic material.
  • the solid support comprises magnetic and nonmagnetic materials.
  • a solid support can comprise a combination of a magnetic material and a nonmagnetic material.
  • the magnetic material is at least about 5, 10, 20, 30, 40, 50, 60, 70, or about 80% by weight of the total composition of the solid support.
  • the bead size can be quite large, on the order of 100-900 microns or in some cases even up to a diameter of 3 mm. In other embodiments, the bead size can be on the order of 1-150 microns.
  • the average particle diameters of beads can be in the range of about 2 m to several millimeters, e.g., diameters in ranges having lower limits of 2 ⁇ m, 4 ⁇ m, 6 ⁇ m, 8 ⁇ m, 10 ⁇ m, 20 ⁇ m, 30 ⁇ m, 40 ⁇ m, 50 ⁇ m, 60 ⁇ m, 70 ⁇ m, 80 ⁇ m, 90 ⁇ m, 100 ⁇ m, 150 ⁇ m, 200 ⁇ m, 300 ⁇ m, or 500 ⁇ m, and upper limits of 20 ⁇ m, 30 ⁇ m, 40 ⁇ m, 50 ⁇ m, 60 ⁇ m, 70 ⁇ m, 80 ⁇ m, 90 ⁇ m, 100 ⁇ m, 150 ⁇ m, 200 ⁇ m, 300 ⁇ m, 500 ⁇ m, 750 ⁇ m, 1 mm, 2 mm, or 3 mm.
  • the support can comprise an array.
  • the array comprises a target analyte.
  • the target analyte comprises a nucleoside, a nucleotide, a polynucleotide, a peptide, a peptoid, a saccharide, a polysaccharide, an aptamer, or an antibody or fragment thereof.
  • the target analyte comprises a library of target analytes.
  • an array comprises a library of molecules.
  • the array can comprise at least about 100, 1000, 10,000, 100,000, 10 6 , 10 7 , 10 8 , 10 9 , 10 10 , 10 11 , 10 12 , 10 13 10 14 , or 10 15 molecules per 1 cm 2 .
  • a molecule can comprise a sequence of monomers.
  • the sequence of monomers can comprise a sequence of amino acids.
  • a feature can be a region on a substrate from about 0.5 microns to about 200 microns in diameter.
  • the array can have a plurality of features. In some embodiments, the center-to-center distance between features can be from about 1 micron to about 300 microns.
  • the array can comprise at least about 1,000, 10,000, 100,000, 200,000, 300,000, 400,000, or 500,000, 1 million, 2 million, 3 million, 4 million, or 8 million features per 1 cm 2 .
  • at least about 40% of the molecules in the library are distinct.
  • at least about 50% of the molecules in the library are distinct.
  • at least about 60% of the molecules in the library are distinct.
  • at least about 70% of the molecules in the library are distinct.
  • at least about 80% of the molecules in the library are distinct.
  • at least about 90% of the molecules in the library are distinct.
  • At least 50% of the molecules in the library are at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, or 100 monomers in length. In some embodiments, at least 50% of the molecules in the library are at most 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, or 100 monomers in length. In some embodiments, the library comprises a median monomer length of about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, or 100 monomers.
  • the array can comprise at least 10,000, 50,000, 100,000, 200,000, 300,000, 400,000, 500,000, 600,000, 700,000, 800,000, 900,000, 10 6 , or 10 7 sequentially distinct library molecules.
  • the array substrate can be selected from wafers, slides, and beads.
  • the library can be an in-situ synthesized chemical library.
  • the molecules can be polynucleotides, peptides, peptoids, or polysaccharides.
  • An analyte binding moiety also referred to as a binding moiety (or domain) can be the region, molecule, domain, portion, fragment, or moiety that binds to a target analyte.
  • a binding moiety confers the ability to bind or specifically bind to given target.
  • a binding moiety can be a nucleic acid molecule or can be proteinaceous.
  • Binding moieties include, but are not limited to, RNAs DNAs, RNA-DNA hybrids, small molecules (e.g., drugs or metabolites), aptamers, polypeptides, proteins, antibodies, viruses, virus particles, cells, fragments thereof, and combinations thereof.
  • a binding moiety can be a polypeptide, a protein, or any fragment thereof.
  • a polypeptide or protein can be an engineered or recombinant polypeptide or protein.
  • a binding moiety is an antibody or fragment thereof.
  • An antibody can be of any isotype (e.g., IgG, IgE, IgM, IgD, IgA and IgY), class (IgG 1 , IgG 2 , IgG 3 , IgG 4 , IgA 1 , IgA 2 ), subclass or modified version thereof.
  • Antibodies may include complete immunoglobulins or fragments thereof.
  • An antibody fragment can refer to one or more fragments of an antibody that retains the ability to specifically bind to a target molecule, such as an antigen.
  • a binding moiety can be an aptamer.
  • An aptamer is an isolated nucleic acid molecule that can bind with high specificity and affinity to a target analyte, such as a protein.
  • An aptamer comprises a three dimensional structure held in certain conformation(s) that provide chemical contacts to specifically bind a given target.
  • a binding moiety is small molecule.
  • a small molecule can be a macrocyclic molecule, an inhibitor, a drug, or chemical compound.
  • a binding moiety is a cell.
  • a binding moiety can be an inact cell, a cell treated with a compound (e.g. a drug), a fixed cell, a lysed cell, or any combination thereof.
  • Detection methods for detecting bound binding moieties can include photometric and non-photometric means.
  • such methods process includes a method to detect and measure absorbance, fluorescence, refractive index, polarization or light scattering. These include direct and/or indirect means to measure such parameters.
  • Methods involving fluorescence include fluorescent tagging in immunological methods such as ELISA or sandwich assay.
  • Methods involving refractive index include surface Plasmon resonance (SPR), grating coupled methods (e.g., sensors uniform grating couplers, wavelength-interrogated optical sensors (WIOS) and chirped grating couplers), resonant minor and interferometric techniques.
  • Methods involving polarization include ellipsometry.
  • Light scattering methods may also be used.
  • Other means for tagging and/or separating and/or detecting can also include magnetic means. Magnetic resonance imaging (MRI), or gas phase ion spectrometry may all be used.
  • MRI Magnetic resonance imaging
  • Non-photometric methods of detection include, without limitation, magnetic resonance imaging, gas phase ion spectrometry, atomic force microscopy and multipolar coupled resonance spectroscopy.
  • Magnetic resonance imaging (MRI) is based on the principles of nuclear magnetic resonance (NMR), a spectroscopic technique used by scientists to obtain microscopic chemical and physical information about molecules.
  • Gas phase ion spectrometers include mass spectrometers, ion mobility spectrometers and total ion current measuring devices.
  • Binding assays can also be useful, e.g., for identifying disease related antibodies (binding moieties) that interact with the target analytes described herein.
  • binding assays can involve, but are not limited to, use of isolated polypeptides, crude extracts, or cell-based assays.
  • the assays described herein can be used to a) identify subjects whose have a first disease or a second disease; (b) assess the impact of an disease therapy; and (c) monitor disease progression.
  • Binding assays can involve contacting a target analyte with a sample comprising a binding moiety (antibody) and allowing sufficient time for the molecule and test agents to form a binding complex. Any binding complexes formed can be detected using any of a number of established analytical techniques.
  • Binding assays include, but are not limited to, methods that measure co-precipitation or co-migration on non-denaturing SDS-polyacrylamide gels, co-migration on Western blots, enzyme linked immunosorbent assay (ELISA), radioimmunoassay (RIA), immunoradiometric assay, fluoroimmunoassay, chemiluminescent assay, bioluminescent assay, fluorescence activated cells sorting (FACS), or fluorescence resonance energy transfer (FRET).
  • ELISA enzyme linked immunosorbent assay
  • RIA radioimmunoassay
  • immunoradiometric assay immunoradiometric assay
  • fluoroimmunoassay chemiluminescent assay
  • bioluminescent assay bioluminescent assay
  • FACS fluorescence activated cells sorting
  • FRET fluorescence resonance energy transfer
  • the methods and apparatus disclosed herein can be used to screen for various diseases or conditions, including an alteration in the state of the body or of some of the organs, interrupting or disturbing the performance of the functions and/or causing symptoms such as discomfort, dysfunction, distress, or even death to the person afflicted or those in contact with the person.
  • a disease or condition can also include a distemper, ailing, ailment, amalady, disorder, sickness, illness, complain, interdisposition and/or affectation.
  • samples containing binding moieties from a diseased animal can be simultaneously screened for the binding moieties' ability to interact with an array. These interactions can be compared to those of samples from individuals that are not in a disease state, not presenting symptoms of persons in the disease state, or presenting symptoms of the disease state.
  • the levels of binding moieties in samples from a diseased animal can be simultaneously determined. These levels can be compared to those of samples from individuals that are not in a disease state, not presenting symptoms of persons in the disease state, or presenting symptoms of the disease state.
  • the methods, kits, and compositions described herein can be used in medical diagnostics, drug discovery, molecular biology, immunology and toxicology.
  • Arrays can be used for large scale binding assays in numerous diagnostic and screening applications.
  • the multiplexed measurement of quantitative variation in levels of large numbers of target analytes (e.g., proteins) allows the recognition of patterns defined by several to many different target analytes.
  • the multiplexed identification of large numbers of interactions between target analytes and binding moieties allows for the recognition of binding and interaction patterns defined by several to many different interactions between target analytes and binding moieties. Many physiological parameters and disease-specific patterns can be simultaneously assessed.
  • One embodiment involves the separation, identification and characterization of proteins present in a biological sample.
  • target analytes can be used as targets for drug development or as molecular markers of disease.
  • Substrate-bound molecules of the present invention may also be used as solid phase filtration devices, wherein capture agents are attached to the surface.
  • methods can be methods for diagnosing or detecting a disease or condition such as a cancer, inflammatory disease, immune disease, autoimmune disease, cardiovascular disease, neurological disease, infectious disease, metabolic disease, or a perinatal condition.
  • a disease or condition such as a cancer, inflammatory disease, immune disease, autoimmune disease, cardiovascular disease, neurological disease, infectious disease, metabolic disease, or a perinatal condition.
  • the disease or condition can be a tumor, neoplasm, or cancer.
  • the cancer can be, but is not limited to, breast cancer, ovarian cancer, lung cancer, colon cancer, hyperplastic polyp, adenoma, colorectal cancer, high grade dysplasia, low grade dysplasia, prostatic hyperplasia, prostate cancer, melanoma, pancreatic cancer, brain cancer (such as a glioblastoma), hematological malignancy, hepatocellular carcinoma, cervical cancer, endometrial cancer, head and neck cancer, esophageal cancer, gastrointestinal stromal tumor (GIST), renal cell carcinoma (RCC) or gastric cancer.
  • the colorectal cancer can be CRC Dukes B or Dukes C-D.
  • the hematological malignancy can be B-Cell Chronic Lymphocytic Leukemia, B-Cell Lymphoma-DLBCL, B-Cell Lymphoma-DLBCL-germinal center-like, B-Cell Lymphoma-DLBCL-activated B-cell-like, or Burkitt's lymphoma.
  • the disease or condition can also be a premalignant condition, such as Barrett's Esophagus.
  • the disease or condition can also be an inflammatory disease, immune disease, or autoimmune disease.
  • the disease may be inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), pelvic inflammation, vasculitis, psoriasis, diabetes, autoimmune hepatitis, Multiple Sclerosis, Myasthenia Gravis, Type I diabetes, Rheumatoid Arthritis, Psoriasis, Systemic Lupus Erythematosis (SLE), Hashimoto's Thyroiditis, Grave's disease, Ankylosing Spondylitis Sjogrens Disease, CREST syndrome, Scleroderma, Rheumatic Disease, organ rejection, Primary Sclerosing Cholangitis, or sepsis.
  • the disease or condition can also be a cardiovascular disease, such as atherosclerosis, congestive heart failure, vulnerable plaque, stroke, or ischemia.
  • the cardiovascular disease or condition can be high blood pressure, stenosis, vessel occlusion or a thrombotic event.
  • the disease or condition can also be a neurological disease, such as Multiple Sclerosis (MS), Parkinson's Disease (PD), Alzheimer's Disease (AD), schizophrenia, bipolar disorder, depression, autism, Prion Disease, Pick's disease, dementia, Huntington disease (HD), Down's syndrome, cerebrovascular disease, Rasmussen's encephalitis, viral meningitis, neuropsychiatric systemic lupus erythematosus (NPSLE), amyotrophic lateral sclerosis, Creutzfeldt-Jacob disease, Gerstmann-Straussler-Scheinker disease, transmissible spongiform encephalopathy, ischemic reperfusion damage (e.g., stroke), brain trauma, microbial infection, or chronic fatigue syndrome.
  • MS Multiple Sclerosis
  • PD Parkinson's Disease
  • AD Alzheimer's Disease
  • AD Alzheimer's Disease
  • AD schizophrenia
  • bipolar disorder depression
  • autism autism
  • Prion Disease Pick's disease
  • dementia Huntington disease
  • Down's syndrome cerebro
  • the condition may also be fibromyalgia, chronic neuropathic pain, or peripheral neuropathic pain.
  • the disease or condition may also be an infectious disease, such as a bacterial, viral or yeast infection.
  • the disease or condition may be Whipple's Disease, Prion Disease, cirrhosis, methicillin-resistant Staphylococcus aureus , HIV, hepatitis, syphilis, meningitis, malaria, tuberculosis, or influenza.
  • the disease or condition can also be a perinatal or pregnancy related condition (e.g., preeclampsia or preterm birth), zika virus, dengue fevor, flavivirus, or a metabolic disease or condition, such as a metabolic disease or condition associated with iron metabolism.
  • methods are methods for diagnosing or detecting an autoimmune disorder.
  • methods can be methods for determining a disease or condition or the progression of a disease or condition.
  • disorder associated with the immune system can include: autoimmune disorders, inflammatory diseases, HIV, rheumatoid arthritis, diabetes mellitus type 1, systemic lupus erythematosus, scleroderma, multiple sclerosis, severe combined immunodeficiency (SCID), DiGeorge syndrome, ataxia-telangiectasia, seasonal allergies, perennial allergies, food allergies, anaphylaxis, mastocytosis, allergic rhinitis, atopic dermatitis, Parkinson's, Alzheimer's, hypersplenism, leukocyte adhesion deficiency, X-linked lymphoproliferative disease, X-linked agammaglobulinemia, selective immunoglobulin A deficiency, hyper IgM syndrome, autoimmune lymphoproliferative syndrome, Wiskot
  • kits that find use in practicing the subject methods, as mentioned above.
  • a kit can include one or more of the compositions described herein.
  • a kit can include at least one nucleoside, nucleotide, polynucleotide, peptide, peptoid, saccharide, aptamer, or antibody or fragment thereof.
  • a kit can include at least one binding moiety.
  • a kit can include a solid support.
  • the solid support is already functionalized with at least one molecule of structure I.
  • the solid support is already functionalized with at least one nucleoside, nucleotide, polynucleotide, peptide, peptoid, saccharide, aptamer, or antibody or fragment thereof.
  • a kit can include a reagent for coupling at least one nucleoside, nucleotide, polynucleotide, peptide, peptoid, saccharide, aptamer, or antibody or fragment thereof to the solid support.
  • kit components may be present in separate containers, or one or more of the components may be present in the same container, where the containers may be storage containers and/or containers that are employed during the assay for which the kit is designed.
  • the subject kits may further include instructions for practicing the subject methods. These instructions may be present in the subject kits in a variety of forms, such as printed information on a suitable medium or substrate (e.g., a piece or pieces of paper on which the information is printed), in the packaging of the kit, in a package insert, etc. Yet another means would be a computer readable medium (e.g., diskette, CD, etc.), on which the information has been recorded. Yet another means that may be present is a website address which may be used via the internet to access the information at a removed site.
  • a suitable medium or substrate e.g., a piece or pieces of paper on which the information is printed
  • a computer readable medium e.g., diskette, CD, etc.
  • a website address which may be used via the internet to access the information at a removed site.
  • Additional embodiments relate to the communication of assay results or diagnoses or both to technicians, physicians or subjects, for example.
  • computers will be used to communicate results of the assessing or diagnoses or both to interested parties, e.g., physicians and their subjects.
  • the assessing can be performed or results analyzed in a country or jurisdiction which differs from the country or jurisdiction to which the results or diagnoses are communicated.
  • a diagnosis based on the presence or absence in a test subject of a binding moiety or a binding signature, or signal identified may be communicated to the subject as soon as possible after the diagnosis is obtained. The diagnosis may be communicated to the subject by the subject's treating physician.
  • the diagnosis may be sent to a test subject by email or communicated to the subject by phone.
  • a computer may be used to communicate the diagnosis by email or phone.
  • the message containing results of a diagnostic test may be generated and delivered automatically to the subject using a combination of computer hardware and software which will be familiar to artisans skilled in telecommunications.
  • all or some of the method steps, including the assaying of samples, diagnosing of diseases, and communicating of method results or diagnoses, may be carried out in diverse (e.g., foreign) jurisdictions.
  • ranges When ranges are present, the ranges include the range endpoints. Additionally, every sub range and value within the rage is present as if explicitly written out.
  • the term “about” or “approximately” can mean within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, e.g., the limitations of the measurement system. For example, “about” can mean within 1 or more than 1 standard deviation, per the practice in the art. Alternatively, “about” can mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value.
  • the term can mean within an order of magnitude, within 5-fold, or within 2-fold, of a value.
  • FIG. 1 illustrates a GPTMS-PAAm molecule.
  • FIG. 2 illustrates a GPTMS-TAEA molecule.
  • FIG. 5 illustrates a GPTMS-HMDA molecule

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